METABOLIC REGULATION OF MYOCARDIAL CONTRACTILITY

本项目的总体目标是确定调节 冠状动脉血流减少时的心肌收缩力。 这一目标 将通过测试以下两部分假设来完成， 离体灌注兔心脏： 冠状动脉流量轻度至中度减少。 在冠状动脉流速下 当氧的可用性不是ATP合成的速率限制时， 在心肌钙瞬变主要调节心肌 收缩性 冠状动脉流量严重减少 在冠状动脉流速下， 可用性是ATP合成的速率限制，无机 磷酸盐（Pi）和/或H+主要通过以下方式调节心肌收缩性： 降低肌丝钙敏感性。 为了验证这一假设，同时测量钙 瞬时，磷酸盐（ATP，磷酸肌酸，Pi），细胞内pH值，和 心肌收缩力将在稳态降低 冠状动脉血流和急性无血流状态。 钙瞬变将是 使用荧光钙指示剂indo-1测量。 磷酸盐和 使用31 P NMR光谱法测量细胞内pH。 拟议 实验将提供新的和重要的信息， 在冠状动脉流量减少期间调节收缩性的机制。

The overall goal of this project is to determine the factors that regulate myocardial contractility during reductions of coronary flow. This goal will be accomplished by testing the following two-part hypothesis in isolated perfused rabbit hearts: .mild to moderate reductions of coronary flow. At coronary flow rates where oxygen availability is not rate-limiting for ATP synthesis, changes in the myocardial calcium transient primarily regulate myocardial contractility. .severe reductions of coronary flow. At coronary flow rates where oxygen availability is rate limiting for ATP synthesis, increases of inorganic phosphate (Pi) and/or H+ primarily regulate myocardial contractility by decreasing myofilament calcium sensitivity. To test this hypothesis, simultaneous measurements of the calcium transient, phosphates (ATP, phosphocreatine, Pi), intracellular pH, and myocardial contractility will be made during steady-state reductions of coronary flow and acute no-flow conditions. The calcium transient will be measured using indo-1, a fluorescent calcium indicator. Phosphates and intracellular pH will be measured using 31P NMR spectroscopy. The proposed experiments will provide new and important information regarding the mechanisms that regulate contractility during reductions of coronary flow.